In clinical practice, however,
creatinine clearance or estimates of creatinine clearance based on the serum creatinine level are used to measure GFR. Creatinine is produced naturally by the body (
creatinine is a breakdown product of
creatine phosphate, which is found in muscle). It is freely filtered by the glomerulus, but also actively
secreted by the peritubular capillaries in very small amounts such that creatinine clearance overestimates actual GFR by 10–20%. This margin of error is acceptable, considering the ease with which creatinine clearance is measured. Unlike precise GFR measurements involving constant infusions of inulin, creatinine is already at a steady-state concentration in the blood, and so measuring creatinine clearance is much less cumbersome. However, creatinine estimates of GFR have their limitations. All of the estimating equations depend on a prediction of the 24-hour creatinine excretion rate, which is a function of muscle mass which is quite variable. The Cockcroft-Gault and CKD-EPI 2021 equations (see below) do not correct for race. With a higher muscle mass, serum creatinine will be higher for any given rate of clearance. A common mistake made when just looking at serum creatinine is the failure to account for muscle mass. Hence, an older woman with a serum creatinine of 1.4 mg/dL may actually have a moderately severe
chronic kidney disease, whereas a young muscular male can have a normal level of renal function at this serum creatinine level. Creatinine-based equations should be used with caution in
cachectic patients and patients with
cirrhosis. They often have very low muscle mass and a much lower creatinine excretion rate than predicted by the equations below, such that a cirrhotic patient with a serum creatinine of 0.9 mg/dL may have a moderately severe degree of chronic kidney disease. Estimated GFR (eGFR) is recommended by clinical practice guidelines and regulatory agencies for routine evaluation of GFR whereas measured GFR (mGFR) is recommended as a confirmatory test when more accurate assessment is required. A number of formulae have been devised to estimate GFR or Ccr values on the basis of serum creatinine levels. Where not otherwise stated serum creatinine is assumed to be stated in mg/dL, not μmol/L—divide by 88.4 to convert from μmol/Lto mg/dL.
Cockcroft–Gault formula A commonly used surrogate marker for the estimation of
creatinine clearance is the Cockcroft–Gault (CG) formula, which in turn estimates GFR in mL/min: It is named after the scientists, the asthmologist (b. 1946) and the nephrologist (1925–2003), who first published the formula in 1976, and it employs serum
creatinine measurements and a patient's weight to predict the creatinine clearance. The formula, as originally published, is: :eC_{Cr} = \frac { \mathrm{(140 - Age)} \ \times \ \text{Mass (in kilograms)} \ \times \ [\text{0.85 if Female}]} {\mathrm{72} \ \times \ [\text{Serum Creatinine (in mg/dL)}]} :This formula expects weight to be measured in
kilograms and creatinine to be measured in mg/dL, as is standard in the US. The resulting value is multiplied by a constant of 0.85 if the patient is female. This formula is useful because the calculations are simple and can often be performed without the aid of a
calculator. When serum creatinine is measured in μmol/L: :eC_{Cr} = \frac { \mathrm{(140 - Age)} \ \times \ \text{Mass (in kilograms)} \ \times \ \text{Constant} } {[\text{Serum Creatinine (in } \mu \mathrm{mol/L)}]} :Where
Constant is for men and for women. One interesting feature of the Cockcroft and Gault equation is that it shows how dependent the estimation of CCr is based on age. The age term is (140 – age). This means that a 20-year-old person (140 – 20 = 120) will have twice the creatinine clearance as an 80-year-old (140 – 80 = 60) for the same level of serum creatinine. The C-G equation assumes that a woman will have a 15% lower creatinine clearance than a man at the same level of serum creatinine.
Modification of diet in renal disease (MDRD) formula Another formula for calculating the GFR is the one developed by the
Modification of Diet in Renal Disease Study Group. Most laboratories in Australia, and the United Kingdom calculate and report the estimated GFR along with creatinine measurements and this forms the basis of diagnosis of
chronic kidney disease. The adoption of the automatic reporting of MDRD-eGFR has been widely criticised. The most commonly used formula is the "4-variable MDRD", which estimates GFR using four variables: serum creatinine, age, ethnicity, and gender. The original MDRD used six variables with the additional variables being the
blood urea nitrogen and
albumin levels. The equations have not been validated in acute renal failure. For creatinine in μmol/L: :\text{eGFR} = \text{32788}\ \times \ [\text{Serum Creatinine}]^{-1.154} \ \times \ \text{Age}^{-0.203} \ \times \text{[1.212 if Black]} \ \times \text{[0.742 if Female]} For creatinine in mg/dL: :\text{eGFR} = \text{186}\ \times \ [\text{Serum Creatinine}]^{-1.154} \ \times \ \text{Age}^{-0.203} \ \times \text{[1.212 if Black]} \ \times \text{[0.742 if Female]} : Creatinine levels in μmol/L can be converted to mg/dL by dividing them by 88.4. The 32788 number above is equal to 186×88.41.154. A more elaborate version of the MDRD equation also includes
serum albumin and
blood urea nitrogen (BUN) levels: :\text{eGFR} = \text{170}\ \times \ [\text{Serum Creatinine}]^{-0.999} \ \times \ \text{Age}^{-0.176} \ \times \text{[0.762 if Female]} \ \times \text{[1.180 if Black]} \ \times \ \text{BUN}^{-0.170} \ \times \ \text{Albumin}^{+0.318} :where the creatinine and blood urea nitrogen concentrations are both in mg/dL. The albumin concentration is in g/dL. These MDRD equations are to be used only if the laboratory has NOT calibrated its serum creatinine measurements to isotope dilution mass spectrometry (IDMS). When IDMS-calibrated serum creatinine is used (which is about 6% lower), the above equations should be multiplied by 175/186 or by 0.94086. Since these formulae do not adjust for body size, results are given in units of mL/min per 1.73 m2, 1.73 m2 being the estimated body surface area of an adult with a mass of 63 kg and a height of 1.7 m.
CKD-EPI formula The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula was first published in May 2009. It was developed in an effort to create a formula more accurate than the MDRD formula, especially when actual GFR is greater than 60 mL/min per 1.73 m2. This is the formula recommended by
NICE in the UK. The 2009 CKD-EPI equation is: :\mathrm{eGFR} = 141\ \times \ \mathrm{\min(SCr/k,1)}^{a} \ \times \ \mathrm{\max(SCr/k,1)}^{-1.209} \ \times \ 0.993^\text{Age} \ \times \text{[1.018 if Female]} \ \times \text{[1.159 if Black]} \ where SCr is serum creatinine (mg/dL), k is 0.7 for females and 0.9 for males, a is −0.329 for females and −0.411 for males, min indicates the minimum of SCr/k or 1, and max indicates the maximum of SCr/k or 1. As separate equations for different populations: For creatinine (IDMS calibrated) in mg/dL: ;Male, not black : If serum creatinine (Scr) ≤ 0.9 :: \mathrm{eGFR} = 141\ \times \ \mathrm{(SCr/0.9)}^{-0.411} \ \times \ 0.993^\text{Age} \ : If serum creatinine (Scr) > 0.9 :: \mathrm{eGFR} = 141\ \times \ \mathrm{(SCr/0.9)}^{-1.209} \ \times \ 0.993^\text{Age} \ ;Female, not black : If serum creatinine (Scr) ≤ 0.7 :: \mathrm{eGFR} = 144\ \times \ \mathrm{(SCr/0.7)}^{-0.329} \ \times \ 0.993^\text{Age} \ : If serum creatinine (Scr) > 0.7 :: \mathrm{eGFR} = 144\ \times \ \mathrm{(SCr/0.7)}^{-1.209} \ \times \ 0.993^\text{Age} \ ;Black male : If serum creatinine (Scr) ≤ 0.9 :: \mathrm{eGFR} = 163\ \times \ \mathrm{(SCr/0.9)}^{-0.411} \ \times \ 0.993^\text{Age} \ : If serum creatinine (Scr) > 0.9 :: \mathrm{eGFR} = 163\ \times \ \mathrm{(SCr/0.9)}^{-1.209} \ \times \ 0.993^\text{Age} \ ;Black female : If serum creatinine (Scr) ≤ 0.7 :: \mathrm{eGFR} = 166\ \times \ \mathrm{(SCr/0.7)}^{-0.329} \ \times \ 0.993^\text{Age} \ : If serum creatinine (Scr) > 0.7 :: \mathrm{eGFR} = 166\ \times \ \mathrm{(SCr/0.7)}^{-1.209} \ \times \ 0.993^\text{Age} \ This formula was developed by Levey et al. The 2009 CKD-EPI formula was suggested to improve cardiovascular risk prediction over the MDRD Study formula in a middle-age population. The 2021 CKD-EPI formula does not include a race coefficient (see discussion below). The 2021 CKD-EPI equation is: :\mathrm{eGFR} = 142\ \times \ \mathrm{\min(SCr/k,1)}^{a} \ \times \ \mathrm{\max(SCr/k,1)}^{-1.209} \ \times \ 0.9938^\text{Age} \ \times \text{[1.012 if Female]} \ where SCr is serum creatinine (mg/dL), k is 0.7 for females and 0.9 for males, a is −0.241 for females and −0.302 for males, min indicates the minimum of SCr/k or 1, and max indicates the maximum of SCr/k or 1. As separate equations for different populations: For creatinine (IDMS calibrated) in mg/dL: ;Male : If serum creatinine (Scr) ≤ 0.9 :: \mathrm{eGFR} = 142\ \times \ \mathrm{(SCr/0.9)}^{-0.302} \ \times \ 0.9938^\text{Age} \ : If serum creatinine (Scr) > 0.9 :: \mathrm{eGFR} = 142\ \times \ \mathrm{(SCr/0.9)}^{-1.2} \ \times \ 0.9938^\text{Age} \ ;Female : If serum creatinine (Scr) ≤ 0.7 :: \mathrm{eGFR} = 143\ \times \ \mathrm{(SCr/0.7)}^{-0.241} \ \times \ 0.9938^\text{Age} \ : If serum creatinine (Scr) > 0.7 :: \mathrm{eGFR} = 143\ \times \ \mathrm{(SCr/0.7)}^{-1.2} \ \times \ 0.9938^\text{Age} \
Mayo Quadratic formula Another estimation tool to calculate GFR is the Mayo Quadratic formula. This formula was developed by Rule et al., The equation is: :\text{eGFR} = \text{exp}{(1.911+ 5.249/[\text{Serum Creatinine}] - 2.114/[\text{Serum Creatinine}]^2 - 0.00686 \ \times \ \text{Age} - \text{[0.205 if Female]})} and for full-term infants
k=0.45 ::For infants and children of age 1 to 12 years,
k=0.55. The method of selection of the constant
k has been questioned as being dependent upon the gold-standard of renal function used (i.e. inulin clearance, creatinine clearance, etc.) and also may be dependent upon the urinary flow rate at the time of measurement. In 2009 the formula was updated to use standardized serum creatinine (recommend
k=0.413) and additional formulas that allow improved precision were derived if serum
cystatin C is measured in addition to serum creatinine.
IDMS standardization effort One problem with any creatinine-based equation for GFR is that the methods used to assay creatinine in the blood differ widely in their susceptibility to non-specific chromogens, which cause the creatinine value to be overestimated. In particular, the MDRD equation was derived using serum creatinine measurements that had this problem. The NKDEP program in the United States has attempted to solve this problem by trying to get all laboratories to calibrate their measures of creatinine to a "gold standard", which in this case is
isotope dilution mass spectrometry (IDMS). In late 2009 not all labs in the U.S. had changed over to the new system. There are two forms of the MDRD equation that are available, depending on whether or not creatinine was measured by an IDMS-calibrated assay. The CKD-EPI equation is designed to be used with IDMS-calibrated serum creatinine values only. ==Normal ranges==